Exosomal microRNA-4661-5p-based serum panel as a potential diagnostic biomarker for early-stage hepatocellular carcinoma
Exosomal microRNA-4661-5p-based serum panel as a potential diagnostic biomarker for early-stage hepatocellular carcinoma
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DOI：
10.1002/cam4.3230
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发表时间：
2020-08-01
期刊：
影响因子：
4
通讯作者：
Eun, Jung Woo
中科院分区：
文献类型：
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作者：
Cho, Hyo Jung;Baek, Geum Ok;Eun, Jung Woo
目前，肝细胞癌（HCC）的可靠血清生物标志物尚未建立，特别是对于早期HCC（单个肿瘤< 2 cm）。我们的目的是研究诊断血清exosomal microRNA（exo-miR）面板的早期肝癌。通过整合分析来自三个不同的人HCC RNA测序数据集的miR表达谱来选择驱动致癌miR（onc-miR）候选物。使用定量实时PCR测量血清外泌体中选定的癌-miR的表达。在测试组群（N = 24）和验证组群（N = 144）中评价血清exo-miR对HCC的诊断性能。使用逻辑回归模型开发血清exo-miR组，并评估其诊断性能。通过整合分析三个不同的RNA测序数据集，鉴定了六个有希望的驱动癌miR，包括miR-25- 3 p、miR-140- 3 p、miR-423- 3 p、miR-1269 a、miR-4661- 5 p和miR-4746- 5 p。在六种候选物中，四种血清exo-miR（miR-25- 3 p、miR-1269 a、miR-4661- 5 p和miR-4746- 5 p）在测试群组中显示出有希望的性能，其中接收操作曲线下的面积（AUROC）>0.8。在我们的验证研究中，血清exo-miR-4661- 5 p可以诊断所有阶段的HCC（AUROC = 0.917），甚至在早期阶段（AUROC = 0.923），具有比其他候选血清exo-miR和血清AFP更高的准确性。由exo-miR-4661- 5 p和exo-miR-4746- 5 p组成的组被鉴定为早期HCC的最准确的生物标志物（AUROC = 0.947，95%置信区间= 0.889-0.980，灵敏度= 81.8%，特异性= 91.7%）。总之，基于exo-miR-4661- 5 p的血清组是早期HCC的有希望的诊断标志物。
Currently, a reliable serum biomarker for hepatocellular carcinoma (HCC) has not been established, particularly for early-stage HCC (single tumor < 2 cm). We aimed to investigate diagnostic serum exosomal microRNA (exo-miR) panel for early-stage HCC. Driver oncogenic miR (onco-miR) candidates were selected by integrative analysis of miR expression profiles from three different RNA sequencing datasets of human HCC. Expressions of selected onco-miRs in serum exosome were measured using quantitative real-time PCR. Diagnostic performances of serum exo-miRs for HCC were evaluated in the test cohort (N = 24) and validation cohort (N = 144). Serum exo-miR panels were developed using a logistic regression model, and their diagnostic performance was evaluated. Six promising driver onco-miRs, including miR-25-3p, miR-140-3p, miR-423-3p, miR-1269a, miR-4661-5p, and miR-4746-5p, were identified by integrative analysis of three different RNA sequencing datasets. Among the six candidates, four serum exo-miRs (miR-25-3p, miR-1269a, miR-4661-5p, and miR-4746-5p) showed promising performance in the test cohort with area under the receiving operator curve (AUROC) >0.8. In our validation study, serum exo-miR-4661-5p could diagnose HCC in all stages (AUROC = 0.917), even in early stage (AUROC = 0.923), with a greater accuracy than other candidate serum exo-miRs and serum AFP. The panel composed of exo-miR-4661-5p and exo-miR-4746-5p was identified as the most accurate biomarker for early-stage HCC (AUROC = 0.947, 95% confidence interval = 0.889-0.980, sensitivity = 81.8%, and specificity = 91.7%). In conclusion, exo-miR-4661-5p-based serum panel is a promising diagnostic marker for early-stage HCC.